Radiosensitizing effect of silencing BRCA1 expression on MDA-MB-231 breast cancer bearing nude mice evaluating by 18F-FLT microPET/CT imaging
10.3760/cma.j.cn321828-20220518-00163
- VernacularTitle:18F－FLT microPET/CT显像评价沉默BRCA1表达对MDA－MB－231乳腺癌裸鼠模型的放疗增敏作用
- Author:
Weitao TAO
1
;
Siqi WANG
;
Yangyang XUE
;
Alei XU
;
Huiqin XU
Author Information
1. 安徽医科大学第一附属医院核医学科，合肥 230022
- Keywords:
Breast neoplasms;
Gene silencing;
BRCA1 protein;
Radiation-sensitizing agents;
Dideoxynucleosides;
Positron-emission tomography;
Tomography, X-ray computed
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2023;43(10):609-614
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the radiosensitizing effect of silencing breast cancer susceptibility gene 1 (shBRCA1) expression on MDA-MB-231 breast cancer bearing nude mice by 3′-deoxy-3′- 18F-fluorothymidine ( 18F-FLT) microPET/CT imaging. Methods:Twenty-four BALB/c nude mice were divided into 4 groups ( n=6 in each group) according to the random number table method, namely negative control (NC) group, NC+ radiotherapy group, shBRCA1 group and shBRCA1+ radiotherapy group. 18F-FLT microPET/CT imaging was performed before and 24 h after radiotherapy. The changes of SUV max before and after radiotherapy were compared among 4 groups, and the total proliferative volume (TPV) of tumors in each group after treatment was also analyzed. The expression of Ki-67 in tumor tissues was analyzed by immunohistochemistry. Data were analyzed by paired t test, one-way analysis of variance, least significant difference t test and Pearson correlation analysis. Results:Breast cancer cells targeting the BRCA1 were constructed. Before radiotherapy, the differences of SUV max among the NC group, NC+ radiotherapy group, shBRCA1 group and shBRCA1+ radiotherapy group were not statistically significant (1.034±0.137, 1.031±0.152, 1.028±0.169 and 1.026±0.156; F=0.00, P=0.999). Twenty-four hours after the end of the four times of radiotherapy, the differences of SUV max among the 4 groups were statistically significant (1.367±0.100, 0.781±0.079, 1.306±0.213 and 0.597±0.129; F=44.77, P<0.001), with lower SUV max in the shBRCA1+ radiotherapy group compared with the NC+ radiotherapy group ( t=2.98, P=0.014). The SUV max of the NC+ radiotherapy group and shBRCA1+ radiotherapy group were reduced compared with those before radiotherapy ( t values: 5.82, 5.44, P values: 0.002, 0.003), while SUV max of the NC group and shBRCA1 group increased compared with those before radiotherapy ( t values: -4.47, -3.98, P values: 0.007, 0.011). TPV was smaller in the shBRCA1+ radiotherapy group compared with that in the NC+ radiotherapy group (0.48±0.03 vs 0.61±0.07; F=25.36, t=3.82, P=0.003). Immunohistochemical assays showed that Ki-67 was less expressed in the shBRCA1+ radiotherapy group than that in the NC+ radiotherapy group (0.286±0.072 vs 0.476±0.093; F=15.73, t=3.61, P=0.007). Correlation analysis showed a positive correlation between Ki-67 expression and SUV max ( r=0.83, P<0.001). Conclusion:18F-FLT microPET/CT imaging can evaluate the radiosensitizing effect of shBRCA1 expression on MDA-MB-231 breast cancer bearing nude mice.
